Mycophenolate Mofetil to Treat Wegener's Granulomatosis and Related Vascular Inflammatory Conditions

NCT00001764 | Completed Phase 1

• 2 other identifiers: 98009298-I-0092
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the safety and effectiveness of the drug mycophenolate mofetil (MPM) in treating Wegener's granulomatosis and related inflammatory vessel diseases. Blood vessel inflammation in these patients may involve different parts of the body, including the brain, nerves, eyes, sinuses, lungs, kidneys, intestinal tract, skin, joints, heart, and other sites. The more severe the involvement, the more likely the disease will be life-threatening. Standard treatment consists of combination drug therapy with prednisone and a cytotoxic agent-usually cyclophosphamide or methotrexate. However, some patients in whom this treatment is initially successful have a disease relapse; other patients cannot take the medications because of other health problems or because of severe side effects of the drugs. MPM is approved by the Food and Drug Administration to prevent kidney transplant rejection. It is chemically similar to another cytotoxic drug called azathioprine, which has been beneficial in maintaining remission in patients with Wegener's granulomatosis who have been treated successfully with cyclophosphamide. Because MPM is more effective than azathioprine in preventing organ rejection, it may also prove beneficial as a second-line treatment for Wegener's granulomatosis. Patients with Wegener's granulomatosis or related inflammatory vessel diseases who have had a relapse following treatment with cyclophosphamide and methotrexate or who cannot take one or both of these drugs may be eligible for this study. Only patients who have been treated at NIH in the methotrexate protocol or the cyclophosphamide switching to methotrexate protocol, or who have received the exact same treatment from their own physician may participate. Participants will have a complete medical evaluation including laboratory studies. Consultations, X-rays and biopsies of affected organs may also be done if indicated for diagnosis or treatment. Patients with active disease will be given MPM and prednisone, both in tablet form. Patients with inactive disease will receive only prednisone if they are already taking it. In both cases, the prednisone will be reduced gradually and discontinued if the disease improves significantly. MPM therapy will continue for at least 2 years. If after 2 years the disease remains in remission, the MPM dose will be gradually reduced and then stopped. If active disease recurs while on MPM therapy, the treatment plan will likely be changed. The new regimen will be determined by the severity of disease, other medical conditions, and history of side effects to previous medications. Patients will be followed at the NIH clinic every month for the first 3 months on MPM and then every 3 months for another 18 months. Those whose disease has remained in remission and have stopped all medications will then be followed every 6 months for 4 visits. The follow-up visits will include a physical examination, blood draws, and, if needed, X-rays. Visits may be scheduled more frequently if medically indicated.

Conditions

Vasculitis; Wegener's Granulomatosis

Keywords

Alternative agent; Purine Antimetabolite; Immunosuppressive; Previous relapse; Drug Intolerance; Wegener's Granulomatosis

Interventions

Mycophenolate Mofetil DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Documentation of Wegener's Granulomatosis (WG) based on clinical characteristics and histopathological evidence of vasculitis.
• Patient with a positive C- or P-ANCA and glomerulonephritis as evidenced by the presence of red blood cell casts and proteinuria or renal biopsy showing necrotizing glomerulonephritis in the absence of positive immunofluorescence for immunoglobulin and complement will also be eligible.
• Patients must be of the ages of 18-80 years.
• Patients on the CYC to MTX protocol (#95-I-0091) who experience a relapse of disease while on MTX maintenance therapy. Relapse is defined by a Vasculitis Disease Activity Index of greater than or equal to 3. Patients from outside the NIH will also be eligible if they have been treated with a CYC to MTX regimen identical to that used in #95-I-0091 and experience a relapse of disease while on MTX maintenance therapy. If treatment for this relapse has already been commenced at the outside institution with daily CYC and glucocorticoid, patients will still be eligible if there is a history of a Vasculitis Disease Activity Index greater than or equal to 3 at the time of CYC and glucocorticoid initiation. Patients who experience a relapse of disease after MTX has been stopped or while tapering the MTX dose (following 2 years of maintenance therapy) will not be eligible.
• Patients with active disease who have a contraindication to MTX therapy will be eligible. Evidence of active disease as defined by a Vasculitis Disease Activity Index of greater than or equal to 3.
• Patients with inactive disease who have a contraindication to CYC and. Evidence of active disease as defined by a Vasculitis Disease Activity Index of greater than or equal to 3.
• Patients with inactive disease on MTX while on the CYC to MTX protocol (95-I-0091) or the MTX protocol (90-I-0086) who develop an contraindication necessitating discontinuation of MTX. Patients from outside the NIH will also be eligible if they similarly develop a contraindication to MTX while on treatment.
• Patients with inactive disease on the CYC protocol (#76-I-0041 or 76-I-0042) who develop a contraindication necessitating CYC discontinuation and also have a contraindication to receiving MTX. Patients from outside the NIH will also be eligible if they similarly develop a contraindication to CYC while on treatment and cannot receive MTX.
• Patients with inactive disease who are receiving treatment with CYC and prednisone in a manner similar to #76-I-0042 will be eligible if they have a contraindication to receiving MTX and have been in remission for less 3 months.

You may not qualify if:

• Evidence of active infection which, in the judgment of the investigator, is of greater danger to the patient than the underlying vasculitis. In those instances in which infection cannot be ruled out by gram stain and culture of secretions or collections of fluid in involved organs, it may be necessary to obtain a biopsy of the affected tissue for microbiological and histopathological studies.
• Patients who are pregnant or who are nursing infants will not be eligible. Fertile women must have a negative pregnancy test within one week prior to study entry and must be using an effective means of birth control.
• Patients with active disease who are eligible for the CYC to MTX protocol (#95-I-0091) or the MTX protocol (#90-I-0086).
• Active peptic ulcer disease.
• Serological evidence of infection with human immunodeficiency virus. A serological determination will be performed within two weeks of beginning study participation.
• Inability to comply with study guidelines.
• Creatinine clearance less than 25ml/min.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institute of Allergy and Infectious Diseases (NIAID)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Simmons WD, Rayhill SC, Sollinger HW. Preliminary risk-benefit assessment of mycophenolate mofetil in transplant rejection. Drug Saf. 1997 Aug;17(2):75-92. doi: 10.2165/00002018-199717020-00001.

  PMID: 9285199 BACKGROUND

• Fulton B, Markham A. Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation. Drugs. 1996 Feb;51(2):278-98. doi: 10.2165/00003495-199651020-00007.

  PMID: 8808168 BACKGROUND

• Goldblum R. Therapy of rheumatoid arthritis with mycophenolate mofetil. Clin Exp Rheumatol. 1993 Mar-Apr;11 Suppl 8:S117-9.

  PMID: 8324935 BACKGROUND

MeSH Terms

Conditions

Vasculitis; Granulomatosis with Polyangiitis

Interventions

Mycophenolic Acid

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: April 1, 1998
• Study Completion: June 1, 2004
• Last Updated: March 4, 2008

Record last verified: 2004-06

Locations

US (1)